ICP-MS Multi-Elemental Analysis of the Human Meninges Collected from Sudden Death Victims in South-Eastern Poland.

Metals perform many important physiological functions in the human body. The distribution of elements in different tissues is not uniform. Moreover, some structures can be the site of an accumulation of essential or toxic metals, leading to multi-directional intracellular damage. In the nervous system, these disorders are especially dangerous. Metals dyshomeostasis has been linked to a variety of neurological disorders which end up leading to permanent injuries. The multi-elemental composition of the human brain is still the subject of numerous investigations and debates. In this study, for the first time, the meninges, i.e., the dura mater and the arachnoid, were examined for their elemental composition by means of inductively coupled plasma mass spectrometry (ICP-MS). Tissue samples were collected post mortem from those who died suddenly as a result of suicide (n = 20) or as a result of injuries after an accident (n = 20). The interactions between 51 elements in both groups showed mainly weak positive correlations, which dominated the arachnoid mater compared to the dura mater. The study showed differences in the distribution of some elements within the meninges in the studied groups. The significant differences concerned mainly metals from the lanthanide family (Ln), macroelements (Na, K, Ca, Mg), a few micronutrients (Co), and toxic cadmium (Cd). The performed evaluation of the elemental distribution in the human meninges sheds new light on the trace metals metabolism in the central nervous system, although we do not yet fully understand the role of the human meninges.

Spinal arachnoid sleeves and their possible causative role in cauda equina syndrome and transient radicular irritation syndrome.

INTRODUCTION: We have previously described arachnoid sleeves around cauda equina nerve roots, but at that time we did not determine whether injections could be performed within those sleeves. The purpose of this observational study was to establish whether the entire distal orifice of a spinal needle can be accommodated within an arachnoid sleeve. MATERIALS AND METHODS: We carefully dissected the entire dural sacs off four fresh cadavers, opened them by longitudinal incision, and immersed them in saline. Under direct vision, we penetrated the cauda equina roots nerves traveling almost vertically downward at 30 locations each with a 27- and a 25-G pencil-point needle (60 punctures total). We captured the images with a stereoscopic camera. RESULTS: The nerve root offered no noticeable resistance to needle entry. Although the arachnoid sleeves could not be identified with the naked eye, they were translucent but visible under microscopy. In 21 of 30 attempts with a 27-gauge needle, and in 20 of 30 attempts with a 25-gauge needle, the distal orifice of the spinal needle was completely within the arachnoid sleeve. CONCLUSION: It seems possible to accommodate the distal orifice of a 25- or a 27-gauge pencil-point spinal needle completely within the space of the arachnoid sleeve. An injection within this sleeve could potentially lead to a neurological syndrome, as we have previously proposed.

Characterization of primary human leptomeningeal cells in 2D culture.

Maintaining the integrity of brain barriers is critical for a healthy central nervous system. While extensive research has focused on the blood-brain barrier (BBB) of the brain vasculature and blood-cerebrospinal fluid barrier (BCSFB) of the choroid plexus, the barriers formed by the meninges have not received as much attention. These membranes create a barrier between the brain and cerebrospinal fluid (CSF), as well as between CSF and blood. Recent studies have revealed that this barrier has been implicated in the development of neurological and immunological disorders. In order to gain a deeper comprehension of the functioning and significance of the meningeal barriers, sophisticated models of these barriers, need to be created. The aim of this paper is to investigate the characteristics of commercially available primary leptomeningeal cells (LMCs) that form the meningeal barriers, in a cultured environment, including their morphology, proteomics, and barrier properties, and to determine whether passaging of these cells affects their behaviour in comparison to their in vivo state. The results indicate that higher passage numbers significantly alter the morphology and protein localisation and expression of the LMCs. Furthermore, the primary cell culture co-stained for S100A6 and E-cadherin suggesting it is a co-culture of both pial and arachnoid cells. Additionally, cultured LMCs showed an increase in vimentin and cytokeratin expression and a lack of junctional proteins localisation on the cell membrane, which could suggest loss of epithelial properties due to culture, preventing barrier formation. This study shows that the LMCs may be a co-culture of pial and arachnoid cells, that the optimal LMC passage range is between passages two and five for experimentation and that the primary human LMCs form a weak barrier when in culture.

Molecular anatomy of adult mouse leptomeninges.

Leptomeninges, consisting of the pia mater and arachnoid, form a connective tissue investment and barrier enclosure of the brain. The exact nature of leptomeningeal cells has long been debated. In this study, we identify five molecularly distinct fibroblast-like transcriptomes in cerebral leptomeninges; link them to anatomically distinct cell types of the pia, inner arachnoid, outer arachnoid barrier, and dural border layer; and contrast them to a sixth fibroblast-like transcriptome present in the choroid plexus and median eminence. Newly identified transcriptional markers enabled molecular characterization of cell types responsible for adherence of arachnoid layers to one another and for the arachnoid barrier. These markers also proved useful in identifying the molecular features of leptomeningeal development, injury, and repair that were preserved or changed after traumatic brain injury. Together, the findings highlight the value of identifying fibroblast transcriptional subsets and their cellular locations toward advancing the understanding of leptomeningeal physiology and pathology.

Unforeseen Complications: A Case of Subdural Anesthesia Post-epidural Insertion.

Subdural anesthesia, although rare, is a significant complication of epidural anesthesia. This case report presents a 28-year-old female patient who developed sudden unconsciousness following epidural anesthesia administration for labor pain. Despite no evident contraindications to epidural anesthesia, she lost consciousness shortly after the initial test dose, leading to an emergency cesarean section under general anesthesia. The neonate showed signs of fetal bradycardia post-epidural and required intensive care. The patient made a complete recovery with no postpartum complications. This report underlines the need for vigilant monitoring and the importance of swift interventions in case of complications arising from epidural anesthesia.

Predicting Arachnoid Membrane Descent in the Chiasmatic Cistern in the Treatment of Pituitary Macroadenoma.

OBJECTIVE: Preoperative prediction of the arachnoid membrane descent in pituitary surgery is useful for achieving gross total removal and avoiding cerebrospinal fluid leakage resulting from tearing of the arachnoid membrane in the chiasmatic cistern. In this study, we analyzed the patterns of arachnoid membrane descent during or after pituitary tumor surgery and identified the factors related to this descent. METHODS: Analysis was restricted to pituitary macroadenomas not extending into the third ventricle or over the internal carotid artery. To minimize confounding factors, patients who underwent revision surgery, those who had a torn arachnoid during operation or small medial diaphragma sellae (DS) opening, and subtotal resections were excluded. We enrolled 41 consecutive patients in this retrospective analysis. The degree of arachnoid descent was categorized using intraoperative videos. Preoperative magnetic resonance findings, including tumor height, suprasellar extension, and variables including DS area and medial opening size, tumor composition, and displacement of the pituitary stalk and gland were evaluated to determine their correlations with arachnoid membrane descent. RESULTS: Arachnoid membrane descent was significantly correlated with DS area and medial opening size. Based on T2-weighted images (T2WI) magnetic resonance (MR) images, tumor composition was significantly associated with arachnoid membrane descent. Other factors were not significantly correlated with arachnoid membrane descent. CONCLUSION: T2WI of tumor composition and preoperative MR imaging of DS area and medial opening provided valuable information regarding arachnoid membrane descent. These parameters may serve as fundamental measures to facilitate complete resection of pituitary macroadenomas.

Optical coherence tomography of cranial dura mater: Microstructural visualization in vivo.

PURPOSE: The study explores microscope integrated optical coherence tomography (OCT) as a intraoperative imaging technique to delineate the microstructural composition of human dura mater cranialis and underlying leptomeninges for surgical guidance. METHODS: OCT volume scans, light microscopic pictures and light microscopic videos of the dura mater were acquired in patients (n = 20) with indication for craniotomy. OCT volume scans and corresponding light microscopic data were analyzed post procedural. Thickness of anatomical structures was measured during this phase. RESULTS: OCT scanning of the human cranial dura mater was feasible during microsurgical dissection. A discrimination of the endosteal and inner meningeal layer of the cranial dura mater was possible in 70 % (n = 14) of the patients. Transdural OCT scans could further demonstrate subdural anatomical structures: subdural space 10 % (n = 2), subarachnoid space in 35 % (n = 7), arachnoid vessels in 80 % (n = 16) and brain cortex in 90 % (n = 16) of the patients. Orthogonal distance measurement was possible. The cranial dura mater showed a mean depth of 216 µm, the endosteal layer of 120 µm and the inner meningeal layer of 132 µm. Imaging quality of the dural segment was high - approaching spatial resolution of histopathology. Imaging quality of subdural segments was lower and demonstrated A-line artifacts in 45 % (n = 7). CONCLUSION: These results illustrate - for the first time - strengths and weaknesses of three dimensional microscope integrated OCT as an in vivo imaging method of the human cranial dura mater, underlying leptomeninges and human brain cortex as a surgical guidance tool. OCT imaging of the cranial dura mater showed extensive details. Transdural imaging of subdural micro anatomical structures was possible, but showed lower image quality with intermittent A-line artifacts. OCT stated the first intraoperative imaging tool to measure the depth of micro anatomical structures with a high spatial resolution of 7,5 µm.

Ultrastructural and Molecular Characterization of Platelet-derived growth factor Beta-Positive Leptomeningeal Cells in the Adult Rat Brain.

The leptomeninges, referring to the arachnoid and pia mater and their projections into the perivascular compartments in the central nervous system, actively participate in diverse biological processes including fluid homeostasis, immune cell infiltrations, and neurogenesis, yet their detailed cellular and molecular identities remain elusive. This study aimed to characterize platelet-derived growth factor beta (PDGFR-ß)-expressing cells in the leptomeninges in the adult rat brain using light and electron microscopy. PDGFR-ß+ cells were observed in the inner arachnoid, arachnoid trabeculae, pia mater, and leptomeningeal sheath of the subarachnoid vessels, thereby forming a cellular network throughout the leptomeninges. Leptomeningeal PDGFR-ß+ cells were commonly characterized by large euchromatic nuclei, thin branching processes forming web-like network, and the expression of the intermediate filaments nestin and vimentin. These cells were typical of active fibroblasts with a well-developed rough endoplasmic reticulum and close spatial correlation with collagen fibrils. Leptomeningeal PDGFR-ß+ cells ensheathing the vasculature in the subarachnoid space joined with pial PDGFR-ß+ cells upon entering the cortical parenchyma, yet perivascular PDGFR-ß+ cells in these penetrating vessels underwent abrupt changes in their morphological and molecular characteristics: they became more flattened with loss of immunoreactivity for nestin and vimentin and deficient collagen deposition, which was indicative of inactive fibroblasts termed fibrocytes. In the cortical parenchyma, PDGFR-ß immunoreactivity was almost exclusively localized to larger caliber vessels, and significantly decreased in capillary-like microvessels. Collectively, our data identify PDGFR-ß as a novel cellular marker for leptomeningeal fibroblasts comprising the leptomeninges and perivascular adventitial cells of the subarachnoid and penetrating large-sized cortical vasculatures.

Meninges: from protective membrane to stem cell niche.

Meninges are a three tissue membrane primarily known as coverings of the brain. More in depth studies on meningeal function and ultrastructure have recently changed the view of meninges as a merely protective membrane. Accurate evaluation of the anatomical distribution in the CNS reveals that meninges largely penetrate inside the neural tissue. Meninges enter the CNS by projecting between structures, in the stroma of choroid plexus and form the perivascular space (Virchow-Robin) of every parenchymal vessel. Thus, meninges may modulate most of the physiological and pathological events of the CNS throughout the life. Meninges are present since the very early embryonic stages of cortical development and appear to be necessary for normal corticogenesis and brain structures formation. In adulthood meninges contribute to neural tissue homeostasis by secreting several trophic factors including FGF2 and SDF-1. Recently, for the first time, we have identified the presence of a stem cell population with neural differentiation potential in meninges. In addition, we and other groups have further described the presence in meninges of injury responsive neural precursors. In this review we will give a comprehensive view of meninges and their multiple roles in the context of a functional network with the neural tissue. We will highlight the current literature on the developmental feature of meninges and their role in cortical development. Moreover, we will elucidate the anatomical distribution of the meninges and their trophic properties in adult CNS. Finally, we will emphasize recent evidences suggesting the potential role of meninges as stem cell niche harbouring endogenous precursors that can be activated by injury and are able to contribute to CNS parenchymal reaction.